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Hye-Eun Choi, Ji-Sun Shin, Dong-Gyu Leem, Soo-Dong Kim, Won-Jea Cho, Kyung-Tae Lee
Previously, we reported that 6-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(6-methylpyridin-2-yl) nicotinamide (DIMN) analogues inhibited the growth of prostate cancer cells as an anti-androgenic compound. In the present study, we evaluated cytotoxic effects of these DIMN derivatives and found that DIMN-26 most potently inhibited the proliferation of the LNCap-LN3 androgen-dependent and DU145 androgen-independent prostate cancer cells through induction of G2/M phase cell cycle arrest and subsequent apoptosis. The G2/M phase arrest was found due to increases in the activation of cdc2 (also known as cyclin-dependent kinase 1, CDK1)/cyclin B1 complex...
October 5, 2016: Chemico-biological Interactions
Solveig Hausken, Rickard Lönner, Claudia Fahlke, Fredrik Spak
Survey of early alcohol  treatment preferences shows higher confidence in face to face meetings Adult men and women (n = 307), working and living in the area of south west Sweden, answered a web based questionnaire where they graded treatment and caregiver preferences while imagining themselves developing an alcohol problem. Alcohol consumption was measured using AUDIT-C. Face-to-face delivered treatment was preferred over telephone or internet based advice. About 53 percent of the men and women considered treatment given by primary health as poor...
October 4, 2016: Läkartidningen
Wolley Mj, Wu A, Xu S, Gordon Rd, Fenton Ra, Stowasser M
BACKGROUND: Distal tubular sodium retention is a potent driver of hypertension, with the thiazide sensitive sodium-chloride cotransporter (NCC) a key player. The upstream modulators of NCC are unclear, but recent evidence has revealed the kinases 'with-no-lysine kinase 4' (WNK4) and 'STE20/SPS1-related, proline alanine-rich kinase' (SPAK) to be involved. The wider role of mineralocorticoids is poorly understood, but animal models implicate aldosterone as a potent regulator, possibly via effects on plasma potassium...
September 2016: Journal of Hypertension
Richard Wainford, Kathryn Walsh
OBJECTIVE: These studies tested the hypothesis that the SNS release of norepinephrine modulates NCC activity via a WNK1 mechanism to contribute to the pathophysiology of salt-sensitive hypertension in rats. DESIGN AND METHOD: Male Sprague-Dawley (SD) rats receiving a continuous s.c. saline or NE (600 ng/min) infusion or naïve Dahl Salt-Resistant (DSR) and Dahl Salt-Sensitive (DSS) rats were fed a 0.6% (NS) or 8% NaCl (HS) diet for 14 or 21 days respectively (N = 6/group)...
September 2016: Journal of Hypertension
Nina Singh, Costi D Sifri, Fernanda P Silveira, Rachel Miller, Kevin S Gregg, Shirish Huprikar, Erika D Lease, Andrea Zimmer, J Stephen Dummer, Cedric W Spak, Christine Koval, David B Banach, Miloni Shroff, Jade Le, Darin Ostrander, Robin Avery, Albert Eid, Raymund R Razonable, Jose Montero, Emily Blumberg, Ahlaam Alynbiawi, Michele I Morris, Henry B Randall, George Alangaden, Jeffrey Tessier, Thomas V Cacciarelli, Marilyn M Wagener, Hsin Yun Sun
Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75...
September 6, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Erika Moreno, Consuelo Plata, Alejandro Rodríguez-Gama, Eduardo R Argaiz, Norma Vázquez, Karla Leyva-Ríos, León Islas, Christopher Cutler, Diana Pacheco-Alvarez, Adriana Mercado, Raquel Cariño, María Castañeda-Bueno, Gerardo Gamba
The thiazide-sensitive Na-Cl cotransporter NCC is the major pathway for salt reabsorption in the mammalian distal convoluted tubule. NCC plays a key role in the regulation of blood pressure. Its inhibition with thiazides constitutes primary baseline therapy for arterial hypertension. However, the thiazide-binding site in NCC is unknown. Mammals have only one gene encoding for NCC. The eel, however, contains a duplicate gene. NCCα is an ortholog of mammalian NCC and is expressed in the kidney. NCCβ is present in the apical membrane of the rectum...
September 1, 2016: Journal of Biological Chemistry
Tsai-Jung Lin, Sung-Sen Yang, Kuo-Feng Hua, Yu-Ling Tsai, Shih-Hua Lin, Shuk-Man Ka
Sterile 20/SPS1-related proline/alanine-rich kinase (SPAK) can stimulate production of proinflammatory cytokines and interact with inflammation-related molecules. However, it has yet to be determined whether SPAK plays a pathophysiological role in the complicated pathological mechanisms of IgA nephropathy (IgAN), which is mainly characterized by mesangial cell (MC) proliferation and is the most common form of glomerulonephritis. In the present study, we examined the pathophysiological role of SPAK in IgAN using a mouse model and cell models...
August 9, 2016: Free Radical Biology & Medicine
Hjördis Högberg, Janna Skagerström, Fredrik Spak, Per Nilsen, Margareta Larsson
BACKGROUND: Antenatal care in Sweden involves a visit in pregnancy week 6-7 for counseling about lifestyle issues, including alcohol. The aim of this study was to investigate alcohol consumption among partners of pregnant women, their motives for changing drinking patterns when becoming a parent and their perceptions of the midwife's counseling about alcohol. METHOD: The study was conducted at 30 antenatal care centers across Sweden in 2009-2010. All partners who accompanied a pregnant women in pregnancy week >17 were asked to participate...
2016: BMC Public Health
David Penton, Jan Czogalla, Agnieszka Wengi, Nina Himmerkus, Dominique Loffing-Cueni, Monique Carrel, Renuga Devi Rajaram, Olivier Staub, Markus Bleich, Frank Schweda, Johannes Loffing
A high dietary potassium (K(+) ) intake causes a rapid dephosphorylation, and hence inactivation, of the thiazide-sensitive NaCl cotransporter (NCC) in the renal distal convoluted tubule (DCT). Based on experiments in heterologous expression systems, it was proposed that changes in extracellular K(+) concentration ([K(+) ]ex ) modulate NCC phosphorylation via a Cl(-) dependent modulation of the WNK-SPAK/OSR1 kinase pathway. We used the isolated perfused mouse kidney technique and ex vivo preparations of mouse kidney slices to test the physiological relevance of this model on native DCT...
July 25, 2016: Journal of Physiology
Hanna Reinholdz, Preben Bendtsen, Fredrik Spak, Ulrika Müssener
Objective. To explore how the perceptions and experiences of working with risky drinkers change over time among primary health care staff during a systematic implementation project. Methods. Qualitative focus group interviews took place before and after the implementation of the project. Results. The staff displayed a positive change during the implementation period with regard to awareness, knowledge, and confidence that led to a change in routine practice. Throughout the project, staff were committed to engaging with risky drinkers and appeared to have been learning-by-doing...
2016: Journal of Addiction
M Keurhorst, P Anderson, M Heinen, Preben Bendtsen, Begoña Baena, Krzysztof Brzózka, Joan Colom, Paolo Deluca, Colin Drummond, Eileen Kaner, Karolina Kłoda, Artur Mierzecki, Dorothy Newbury-Birch, Katarzyna Okulicz-Kozaryn, Jorge Palacio-Vieira, Kathryn Parkinson, Jillian Reynolds, Gaby Ronda, Lidia Segura, Luiza Słodownik, Fredrik Spak, Ben van Steenkiste, Paul Wallace, Amy Wolstenholme, Marcin Wojnar, Antoni Gual, M Laurant, M Wensing
BACKGROUND: Brief interventions in primary healthcare are cost-effective in reducing drinking problems but poorly implemented in routine practice. Although evidence about implementing brief interventions is growing, knowledge is limited with regard to impact of initial role security and therapeutic commitment on brief intervention implementation. METHODS: In a cluster randomised factorial trial, 120 primary healthcare units (PHCUs) were randomised to eight groups: care as usual, training and support, financial reimbursement, and the opportunity to refer patients to an internet-based brief intervention (e-BI); paired combinations of these three strategies, and all three strategies combined...
2016: Implementation Science: IS
Martin J Wolley, Aihua Wu, Shengxin Xu, Richard D Gordon, Robert A Fenton, Michael Stowasser
Distal tubular sodium retention is a potent driver of hypertension, and the thiazide-sensitive sodium-chloride cotransporter (NCC) has a key role in this process. In humans, factors regulating NCC are unclear, but in animal models, aldosterone is a potent regulator, possibly via effects on plasma potassium. We studied the effects of the mineralocorticoid fludrocortisone on the abundance of NCC and its phosphorylated form (pNCC) as well as WNK lysine deficient protein kinase 4 (WNK4) and STE20/SPS1-related, proline alanine-rich kinase (SPAK) in human urinary exosomes...
July 5, 2016: Journal of the American Society of Nephrology: JASN
Emma Spak
No abstract text is available yet for this article.
2016: Läkartidningen
Eduardo R Argaiz, Gerardo Gamba
PURPOSE OF REVIEW: Abundant evidence supports that the NaCl cotransporter (NCC) activity is tightly regulated by the with-no-lysine (WNK) kinases. Here, we summarize the data regarding NCC regulation by WNKs, with a particular emphasis on WNK4. RECENT FINDINGS: Several studies involving in-vivo and in-vitro models have provided paradoxical data regarding WNK4 regulation of the NCC. Although some studies show that WNK4 can activate the NCC, other equally compelling studies show that WNK4 inhibits the NCC...
September 2016: Current Opinion in Nephrology and Hypertension
Xiao-Yu Shi, Li-Li Zhang, Feng Wu, Yang-Yong Fu, Shang-Jun Yin, Yue-Xiu Si, Yong-Doo Park
Arginine kinase plays an important role in cellular energy metabolism and is closely related to the environmental stress response in marine invertebrates. We studied the Cu(2+)-mediated inhibition and aggregation of Sepia pharaonis arginine kinase (SPAK) and found that Cu(2+) markedly inhibited the SPAK activity along with mixed-type inhibition against the arginine substrate and noncompetitive inhibition against the ATP cofactor. Spectrofluorimetry results showed that Cu(2+) induced a tertiary structure change in SPAK, resulting in exposure of the hydrophobic surface and increased aggregation...
October 2016: International Journal of Biological Macromolecules
Xiangyu Zhou, Isao Naguro, Hidenori Ichijo, Kengo Watanabe
BACKGROUND: Osmotic stress arises from the difference between intracellular and extracellular osmolality. It induces cell swelling or shrinkage as a consequence of water influx or efflux, which threatens cellular activities. Mitogen-activated protein kinases (MAPKs) play central roles in signaling pathways in osmotic stress responses, including the regulation of intracellular levels of inorganic ions and organic osmolytes. SCOPE OF REVIEW: The present review summarizes the cellular osmotic stress response and the function and regulation of the vertebrate MAPK signaling pathways involved...
September 2016: Biochimica et Biophysica Acta
Peter Anderson, Preben Bendtsen, Fredrik Spak, Jillian Reynolds, Colin Drummond, Lidia Segura, Myrna N Keurhorst, Jorge Palacio-Vieira, Marcin Wojnar, Kathryn Parkinson, Joan Colom, Karolina Kłoda, Paolo Deluca, Begoña Baena, Dorothy Newbury-Birch, Paul Wallace, Maud Heinen, Amy Wolstenholme, Ben vanSteenkiste, Artur Mierzecki, Katarzyna Okulicz- Kozaryn, Gaby Ronda, Eileen Kaner, Miranda G H Laurant, Simon Coulton, Toni Gual
AIM: To test if training and support, financial reimbursement and option of referring screen-positive patients to an internet-based method of giving advice (eBI) can increase primary health-care providers' delivery of Alcohol Use Disorders Identification Test (AUDIT)-C-based screening and advice to heavy drinkers. DESIGN: Cluster randomized factorial trial with 12-week implementation and measurement period. SETTING: Primary health-care units (PHCU) in different locations throughout Catalonia, England, the Netherlands, Poland and Sweden...
May 30, 2016: Addiction
D Breiva, I Tracums, I Jaunalksne, D Krievins, A Bistrova, A Spaks
No abstract text is available yet for this article.
April 2016: Journal of Thoracic Oncology
Adriana Mercado, Paola de Los Heros, Zesergio Melo, María Chávez-Canales, Adrián R Murillo-de-Ozores, Erika Moreno, Silvana Bazúa-Valenti, Norma Vázquez, Juliette Hadchouel, Gerardo Gamba
The K(+)-Cl(-) cotransporters (KCC1-KCC4) encompass a branch of the SLC12 family of electroneutral cation-coupled chloride cotransporters that translocate ions out of the cell to regulate various factors, including cell volume and intracellular chloride concentration, among others. L-WNK1 is an ubiquitously expressed kinase that is activated in response to osmotic stress and intracellular chloride depletion, and it is implicated in two distinct hereditary syndromes: the renal disease pseudohypoaldosteronism type II (PHAII) and the neurological disease hereditary sensory neuropathy 2 (HSN2)...
July 1, 2016: American Journal of Physiology. Cell Physiology
Emma Spak
No abstract text is available yet for this article.
2016: Läkartidningen
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